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They analyze a new pathway for the treatment of Sézary syndrome

Blocking specific cellular signaling pathways may be an effective approach to treating this type of cutaneous lymphoma. One of its characteristics is its high genetic and molecular heterogeneity, which makes it difficult to find therapeutic targets. Now, a study published in the Journal of Investigative Dermatology may help to address this.

The Sézary syndrome is a rare and aggressive type of cutaneous T-cell lymphoma that affects the skin. One of its characteristics is its high genetic and molecular heterogeneity. This makes it difficult to identify therapeutic genetic targets to treat it. For this reason, a team led by researchers from the Dermatology Service at Hospital del Mar and from the Research Group on Molecular Mechanisms of Cancer and Stem Cells at the Hospital del Mar Research Institute has analyzed a new way to approach treatment: the routes through which cells are acted upon so that they respond—the signaling pathways.

The study, published in the Journal of Investigative Dermatology, used an animal model to evaluate personalized treatments in patients with Sézary syndrome. Using blood samples from seven patients, inhibitors were applied based on specific signaling pathways that had been found to be altered in in vitro studies. The research team found that, despite the great genetic variability of this disease, only a limited number of signaling pathways are functionally altered, making them potential therapeutic targets.

"This is a treatment directed at an individualized transcriptomic signature of the patient; that is, we select which treatment may be effective according to a signaling pathway that is altered in them", explains Dr. Fernando Gallardo, Head of the Dermatology Service at Hospital del Mar. The results point to a new personalized route for each patient to treat Sézary syndrome.

Members of the Pathology, Nephrology, and Pharmacy services at Hospital del Mar, as well as research staff from the CIBER oncology area (CIBERONC), took part in the work.

Reference article

Andrades E, Iglesias A, Maqueda M, Lobo-Jarne T, González J, Bertran J, Conde D, Rodriguez E, Bellosillo B, Pujol RM, Bigas A, Espinosa L, Gallardo F. Diverse transcriptomic and mutational patterns but limited functional pathway alterations in patient-derived Sézary syndrome cells. J Invest Dermatol. 2026 Feb 3:S0022-202X(26)00067-9. doi: 10.1016/j.jid.2026.01.018. Epub ahead of print. PMID: 41644084.

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